Jiangsu Engineering Laboratory of Novel Functional Polymeric Materials, Jiangsu Key Laboratory of Advanced Negative Carbon Technologies College of Chemistry, Suzhou Key Laboratory of Soft Material and New Energy, College of Chemistry, Chemical Engineering and Materials Science, Soochow University, Suzhou, 215123, China.
Biomater Sci. 2023 May 2;11(9):3114-3127. doi: 10.1039/d2bm02096c.
Poor permeation of therapeutic agents and similar eukaryotic cell metabolic and physiological properties of fungi and human cells are two major challenges that lead to the failure of current therapy for fungi-induced skin and soft tissue infections. Herein, a nitric oxide (NO)-releasing poly(ionic liquid)-based microneedle (PILMN-NO) with the capacity of deep persistent NO toward subcutaneous fungal bed is presented as a synergistic antifungal treatment strategy to treat subcutaneous fungal infection. Upon the insertion of PILMN-NO into skin, the contact fungicidal activities induced by electrostatic and hydrophobic effects of poly(ionic liquid) and the released NO sterilization resulting from the peroxidation and nitrification effect of NO achieved enhanced antifungal efficacy against fungi () both and . Simultaneously, PILMN-NO showed biofilm ablation ability and efficiently eliminated mature biofilms. fungal-induced subcutaneous abscess studies revealed that PILMN-NO could effectively sterilize fungi while suppressing the inflammatory reaction, facilitating collagen deposition and angiogenesis, and promoting wound healing. This work provides a new strategy to overcome the difficulties in deep skin fungal infection treatment and has potential for further exploitation of NO-releasing microbicidal therapy.
治疗药物渗透不良以及真菌和人类细胞类似的真核细胞代谢和生理特性，是导致目前真菌性皮肤和软组织感染治疗失败的两大挑战。在此，我们提出了一种具有持续深层一氧化氮（NO）释放能力的基于聚离子液体的微针（PILMN-NO），作为一种协同抗真菌治疗策略，用于治疗皮下真菌感染。当 PILMN-NO 插入皮肤时，聚离子液体的静电和疏水性诱导的接触杀菌活性和 NO 的释放灭菌（由于 NO 的过氧化和硝化作用），实现了对真菌的增强抗真菌功效（）和。同时，PILMN-NO 表现出生物膜消融能力，并能有效消除成熟的生物膜。真菌性皮下脓肿研究表明，PILMN-NO 能够有效杀灭真菌，同时抑制炎症反应，促进胶原沉积和血管生成，促进伤口愈合。这项工作为克服深部皮肤真菌感染治疗的困难提供了一种新策略，并且具有进一步开发 NO 释放杀菌治疗的潜力。
